The Na pump/Na,K-ATPase is a basic component of the cell membrane and plays a vital role in regulation of the ionic environment of the body. Ample evidence exists that Na pump function is impaired in diabetes mellitus leading to dysfunction of peripheral nerves and possibly other tissues, such as the retina, heart and kidney. Three molecular forms of the Na pump have been described in rats and five in humans. These "isoenzymes" differ in their responses to changes in the ionic environment, to inhibitors such as digitalis-type drugs, and to activation by insulin. The relatively low levels of insulin that are occasionally present in diabetes mellitus - particularly in poorly-controlled disease - lead to understimulation of the insulin-activated isoenzyme and may cause chronic alterations in its synthesis. Specific monoclonal antibodies that recognize each of the isoforms of the Na pump catalytic subunit will be used in immunoprecipitation protocols to determine isoform abundance and synthesis rates in key tissues of the diabetic BB/Wor rat during chronic diabetes. Euglycemia and aldose reductase inhibitor (e.g., Sorbinil) will be employed in separate attempts to block or reverse the Na pump changes in chronic diabetes. As these antibodies also have affinity for both human and mouse Na pump isoforms, non-obese insulin-dependent diabetic mice (NOD) will be examined and tissues will be requested from the National Disease Research Interchange to extend the study to human diabetes. The results will assist in defining the Na pump defect in diabetes and aid in designing a protocol to prevent or diminish the accompanying degenerative changes. The graduate student will study isoform abundance and synthesis rates in one of the tissues under investigation. The undergraduate student will study isoform abundance and enzyme activity. Both students will participate in care of the insulin-dependent rats.